GLP-1 receptor agonists were associated with significantly lower major adverse cardiovascular events and inflammatory biomarkers in patients, regardless of body mass index or glycated hemoglobin.
Do GLP-1 receptor agonists reduce atherosclerosis progression, inflammatory biomarkers, and MACE irrespective of hyperglycemia and obesity?
GLP-1 receptor agonists reduce atherosclerosis progression and inflammation independent of their glucose-lowering and weight-loss effects, translating to lower MACE risk.
Absolute Event Rate: 0% vs 0%
Abstract Background and Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events. However, their impact on atherosclerosis and inflammation, regardless of diabetes or obesity, is unknown. Here, GLP-1 RA effects were investigated on (i) atherosclerosis burden and inflammation in vivo in rabbits and (ii) inflammatory biomarkers and major adverse cardiovascular events (MACE) in clinical subjects, adjusted for glycaemic and obesity status. Methods Rabbits with atherosclerosis received liraglutide (0.1 mg/kg/day) or saline for 4 weeks. Serial intravascular ultrasound (IVUS) and near-infrared fluorescence-optical coherence tomography (NIRF-OCT) assessed plaque burden and cathepsin activity. Histological, plasma, and in vitro analyses assessed GLP-1 RA effects on atheroinflammation. A clinical study of 47,324 participants from the Mass General Brigham Biobank evaluated the association between GLP-1 RA prescription and inflammatory biomarkers lymphocyte-based ratios and C-reactive protein (CRP), and MACE. Analyses included multivariable regression, propensity score matching (PSM), and mediation analysis. Results In 28 normoglycaemic, non-obese rabbits, liraglutide significantly inhibited atherosclerosis progression compared with controls IVUS Δ percent atheroma volume: −7.8%, 95% confidence interval (CI) −11.3 to −4.2; P .001, and reduced NIRF-OCT plaque cathepsin activity (−9.8 nM, 95% CI −18.5 to −1.1; P = .028). Liraglutide further reduced plaque cathepsin S, macrophage content, and plasma CRP levels. In vitro, multiple GLP-1 RAs suppressed cathepsin activity and inflammatory mediators in macrophages. In biobank patients, GLP-1 RA prescription associated with significantly lower levels of inflammatory biomarkers and MACE in regression and PSM analyses, with benefits persisting in subgroups stratified by body mass index or glycated haemoglobin. Mediation analysis showed inflammatory biomarkers partly contributed to this effect. Conclusions This integrative preclinical–clinical study demonstrates that GLP-1 RAs reduce atherosclerosis progression, inflammatory biomarkers and MACE, irrespective of hyperglycaemia or obesity.
“Beyond glucose and weight loss: GLP-1 RAs reduce systemic inflammation, atherosclerosis inflammation and progression, and MACE —independent of diabetes or obesity. ... Time to investigate GLP-1RAs in all patients with CAD?”
Kassab et al. (Fri,) reported a other. GLP-1 receptor agonists were associated with significantly lower major adverse cardiovascular events and inflammatory biomarkers in patients, regardless of body mass index or glycated hemoglobin.